Molecular Biology and Cytogenetics of CML

CML is a clonal disorder that is usually easily diagnosed
because the leukemic cells of more than 95% of patients have a distinctive
cytogenetic abnormality, the Philadelphia chromosome (Ph1).[2,3] The Ph1
results from a reciprocal translocation between the long arms of
chromosomes 9 and 22 and is demonstrable in all hematopoietic precursors.[4]
This translocation results in the transfer of the Abelson (ABL) on chromosome 9 oncogene to an
area of chromosome 22 termed the breakpoint cluster region (BCR).[4] This, in
turn, results in a fused BCR/ABL gene and in the production of an abnormal
tyrosine kinase protein that causes the disordered myelopoiesis found in CML.
Furthermore, these molecular techniques can now be used to supplement
cytogenetic studies to detect the presence of the 9;22 translocation in
patients without a visible Ph1 (Ph1-negative).

Prognosis and Survival

Ph1-negative CML is a poorly defined
entity that is less clearly distinguished from other myeloproliferative
syndromes. Patients with Ph1-negative CML generally have a poorer response to treatment
and shorter survival than Ph1-positive patients.[5] Ph1-negative patients who have BCR/ABL
gene rearrangement detectable by Southern blot analysis, however, have prognoses
equivalent to Ph1-positive patients.[6,7]

Diagnosis

A small subset of patients have BCR/ABL
detectable only by reverse transcriptase–polymerase chain reaction (RT–PCR),
which is the most sensitive technique currently available. Patients with RT–PCR evidence of the BCR/ABL fusion gene appear clinically and prognostically
identical to patients with a classic Ph1; however, patients who are
BCR/ABL-negative by RT–PCR have a clinical course more consistent with chronic
myelomonocytic leukemia, which is a distinct clinical entity related to myelodysplastic
syndrome.[6,8,9] Fluorescent in situ hybridization of the BCR/ABL translocation can be performed on the bone marrow aspirate or on the peripheral blood of patients with CML.[10]

At the time of diagnosis of patients with CML, splenomegaly is the most common finding on physical examination.[10] The spleen may be enormous, filling most of the abdomen and
presenting a significant clinical problem, or the spleen may be only minimally
enlarged. In about 10% of patients, the spleen is neither palpable nor
enlarged on splenic scan.

The median age of patients with Ph1-positive CML is 67 years.[11] While the median survival used to be 4 to 6 years, with the advent of the new oral therapies, the median survival is expected to approach normal life expectancy for most patients, although it is still too soon to say this definitively.

Stage Information for CML

Bone marrow sampling is done to assess cellularity, fibrosis, and cytogenetics.
The Philadelphia chromosome (Ph1) is usually more readily apparent in marrow
metaphases than in peripheral blood metaphases; in some cases, it may be
mashed and reverse transcriptase–polymerase chain reaction (RT–PCR) or fluorescent in situ hybridization analyses on blood or marrow aspirates may be necessary to demonstrate the 9;22
translocation.

Histopathologic examination of bone marrow aspirate demonstrates a shift in the
myeloid series to immature forms that increase in number as patients progress
to the blastic phase of the disease. The marrow is hypercellular, and
differential counts of both marrow and blood show a spectrum of mature and
immature granulocytes similar to that found in normal marrow. Increased
numbers of eosinophils or basophils are often present, and sometimes
monocytosis is seen. Increased megakaryocytes are often found in the marrow,
and sometimes fragments of megakaryocytic nuclei are present in the blood,
especially when the platelet count is very high. The percentage of lymphocytes
is reduced in both the marrow and blood in comparison with normal subjects, and
the myeloid/erythroid ratio in the marrow is usually greatly elevated. The
leukocyte alkaline phosphatase enzyme is either absent or markedly reduced in
the neutrophils of patients with chronic myelogenous leukemia (CML).[1]

Transition from the chronic phase to the accelerated phase and later the blastic
phase may occur gradually over a period of 1 year or more, or it may appear
abruptly (blast crisis). The annual rate of progression from chronic phase
to blast crisis is 5% to 10% in the first 2 years and 20% in subsequent
years.[2,3] Signs and symptoms commonly indicating such a change include the following:

Progressive leukocytosis.

Thrombocytosis or thrombocytopenia.

Anemia. (Refer to the PDQ summary on Fatigue for more information on anemia.)

Detection of the BCR/ABL translocation by RT–PCR during prolonged remissions does not constitute relapse on its own. However, exponential drops in quantitative RT–PCR measurements for 3 to 12 months correlates with the degree of cytogenetic response, just as exponential rises may be associated with quantitative RT–PCR measurements that are closely connected with clinical relapse.[10]

Treatment Option Overview for CML

Treatment of patients with chronic myelogenous leukemia (CML) is usually initiated when the
diagnosis is established, which is done by the presence of an elevated white
blood cell (WBC) count, splenomegaly, thrombocytosis, and identification of the BCR/ABL (breakpoint cluster region/Abelson) translocation.[1] The optimal frontline treatment for patients with chronic-phase CML is the subject of active clinical evaluation but involves specific inhibitors of the BCR/ABL tyrosine kinase.

In a randomized trial comparing imatinib mesylate with interferon plus cytarabine, with 5 years' median follow-up, imatinib mesylate induced complete cytogenetic responses in more than 80% of newly diagnosed patients; in addition, the annual rate of progression to accelerated phase or blast crisis dropped from 2% to less than 1% in the fourth year on the imatinib arm.[2][Level of evidence: 1iiDiii] However, most of these continually responding patients still showed detectable evidence of the BCR/ABL translocation by the most sensitive measurement of reverse transcriptase–polymerase chain reaction (RT–PCR).[3-5] The clinical implication of this finding after 10 years or more is unknown, but these results have changed clinical practice. Although evidence-based survival advantages are unavailable because of crossover in randomized trials, the overall survival rate for all patients at 5 years is 89%, with fewer than 50% of all deaths (4.5%) caused by CML.[6]

Tyrosine kinase inhibitors with greater potency and selectivity than imatinib for BCR/ABL have been evaluated in newly diagnosed patients with CML. In a randomized, prospective study of 846 patients comparing nilotinib with imatinib, the rate of major molecular response at 24 months was 71% and 67% for two-dose schedules of nilotinib and 44% for imatinib (P < .0001 for both comparisons).[7][Level of evidence: 1iiDiv] Progression to accelerated-phase CML or blast crisis occurred in 17 patients on imatinib (14%), but this progression occurred in only two patients (<1%, P = . 0003) and in five patients (<1.8%, P = .0089), respectively, on two-dose schedules of nilotinib.[7]

Similarly, in a randomized, prospective study of 519 patients comparing dasatinib with imatinib, the rate of major molecular response at 12 months was 46% for dasatinib and 28% for imatinib (P < .0001). The rate of major molecular response at 24 months was 64% for dasatinib and 46% for imatinib (P < .0001).[8][Level of evidence: 1iiDiv] Progression to accelerated-phase CML or blast crisis occurred in 13 patients (5%) on imatinib and in six patients (2.3%) on dasatinib (not statistically different).[8]

Although one of these two studies showed statistically significant decreased rates of progression to accelerated or blastic phase, which may ultimately translate into improved survival, the follow-up period with nilotinib and dasatinib has not been long enough to detect and confirm this prolonged survival with these agents. The preferred initial treatment for newly diagnosed patients with chronic-phase CML could be any of these specific inhibitors of the BCR/ABL tyrosine kinase.[9]

The only consistently successful curative treatment of CML beyond 10 years' follow-up has been allogeneic bone marrow transplantation (BMT) or stem cell transplantation (SCT).[10] Long-term data beyond 10 years of therapy are available, and most long-term survivors show no evidence of the BCR/ABL translocation by any available test (e.g., cytogenetics, RT–PCR, or fluorescent in situ hybridization [FISH]). Many patients, however, are not eligible for this approach because of age, comorbid conditions, or lack of a suitable donor. In addition, substantial morbidity and mortality result from allogeneic BMT or SCT; a 15% to 30% treatment-related mortality can be expected, depending on whether a donor is related and on the presence of mismatched antigens.[10]

Long-term data are also available for patients treated with interferon alpha.[11-13] Approximately 10% to 20% of these patients have a complete cytogenetic response with no evidence of BCR/ABL translocation by any available test, and the majority of these patients are disease free beyond 10 years.[10] Maintenance of therapy with interferon is required, however, and some patients experience side effects that preclude continued treatment.

Newly diagnosed patients with very high levels of circulating leukocytes (WBC >100,000/mm3) require immediate therapy with imatinib mesylate to avoid cerebrovascular events or death from leukostasis. Leukophoresis and plateletpheresis are sometimes required for an even more emergent reduction of counts.

Treatment Options for Chronic-Phase CML

Splenectomy may be required and useful in patients having hematologic
problems and physical discomfort from a massive spleen.

Targeted therapy with tyrosine kinase inhibitors

A trial randomly assigning 1,106 previously untreated patients to imatinib mesylate or to interferon plus cytarabine documented a 76% complete cytogenetic response rate with imatinib mesylate versus 14% for interferon plus cytarabine at a median follow-up of 19 months.[1,2][Level of evidence: 1iiDiii] At 18 months, 96.7% of the imatinib group had avoided progression to accelerated-phase chronic myelogenous leukemia (CML) or blast crisis compared with 91.5% of the interferon plus cytarabine group (P < .001). Because 90% of the combination group had switched to imatinib by 18 months (mostly because of intolerance of side effects), a survival difference may never be observed. By the 5-year median follow-up of this trial, imatinib mesylate induced complete cytogenetic response in more than 80% of the participants, with the annual rate of progression to accelerated-phase CML or blast crisis dropping from 2% in the first year to less than 1% in the fourth year.[2] In addition, the overall survival (OS) rate for all patients at 5 years is 89%, with fewer than 50% of all deaths (4.5%) caused by CML. More than 90% of completely responding patients still show detectable evidence of the BCR/ABL translocation, usually by reverse transcription-polymerase chain reaction (RT–PCR) or by fluorescence in situ hybridization of progenitor cell cultures.[3-5] The clinical implication of this finding after 10 years or more is unknown, but these results have changed clinical practice. Poor compliance is the predominant reason for inadequate molecular response to imatinib.[6]

Tyrosine kinase inhibitors with greater potency and selectivity for BCR/ABL than imatinib have been evaluated in newly diagnosed patients with CML. In a randomized, prospective study of 846 patients that compared nilotinib with imatinib, the rate of major molecular response at 24 months was 71% and 67% for two-dose schedules of nilotinib and 44% for imatinib (P < .0001 for both comparisons).[7][Level of evidence: 1iiDiv] Progression to accelerated-phase CML or blast crisis occurred in 17 patients on imatinib (14%), but this progression only occurred in two patients (<1%, P = .0003) and in five patients (1.8%, P = .0089), respectively, for those patients on two-dose schedules of nilotinib.[7] Nilotinib-treated patients had a lower rate of treatment-emergent BCR/ABL mutations than did imatinib-treated patients.[8]

Similarly, in a randomized, prospective study of 519 patients that compared dasatinib with imatinib, the rate of major molecular response at 12 months was 46% for dasatinib and 28% for imatinib (P < .0001). The rate of major molecular response at 24 months was 64% for dasatinib and 46% for imatinib (P < .0001).[9][Level of evidence: 1iiDiv] Progression to accelerated-phase CML or blast crisis occurred in 13 patients (5%) on imatinib and in six patients (2.3%) on dasatinib (not statistically different).[9]

Although one of these two studies showed statistically significant decreased rates of progression to accelerated- or blastic-phase CML, which may ultimately translate into improved survival, the follow-up period with nilotinib and dasatinib has not been long enough to detect and confirm prolonged survival with these agents. In randomized prospective trials (NCT00471497 and NCT00481247), nilotinib and dasatinib show higher rates of earlier molecular response compared with imatinib; whether this will translate to improved long-term outcomes is unclear.[10,11][Level of evidence: 1iiDiv] The preferred initial treatment for newly diagnosed patients with chronic-phase CML could be any of these specific inhibitors of the BCR/ABL tyrosine kinase.[12]

A BCR/ABL transcript level of less than 10% in patients after 3 months of treatment with a specific tyrosine kinase inhibitor is associated with the best prognosis in terms of failure-free survival, progression-free survival (PFS), and OS.[10,11,13-16] However, in a retrospective analysis, even patients with a BCR/ABL transcript level greater than 10% after 3 months of therapy did well when the halving time was less than 76 days.[17] Mandating a change of therapy based on this 10% transcript level at 3 to 6 months is problematic because 75% of patients do well even with a suboptimal response.[18]

Higher doses of imatinib mesylate, alternative tyrosine kinase inhibitors (such as dasatinib or nilotinib, and allogeneic SCT) are implemented for suboptimal response or progression and are under clinical evaluation as frontline approaches.[19-23] Dose escalation of imatinib can be considered for patients with suboptimal response, but clinical trials are required to establish the relative efficacy and sequencing of dose escalation versus the use of dasatinib or nilotinib.[20,21] Two studies looked at dose escalation of imatinib in almost 200 previously untreated patients, most of whom were of intermediate Sokal risk; 63% to 73% achieved a major molecular response by 18 to 24 months and only three patients showed progression to advanced phase in these preliminary phase II results.[24,25][Level of evidence: 3iiiDiv] Until randomized studies are performed, it is unclear whether the increased response with increased dosage will translate into longer durations of response or survival advantages.[22,26]

A single-center, retrospective analysis of 483 patients with chronic phase CML who were treated with imatinib (400 mg or 800 mg daily), dasatinib, or nilotinib indicated that patients who have better than 35% t(9;22)+ cells at 3 months of therapy have inferior event-free, transformation-free, and OS rates compared with patients who have better early cytogenetic responses.[27]

Among the many unanswered questions are the following:

Will responses on tyrosine kinase inhibitors be durable beyond 10 years, and can we ever stop treatment with them? In a prospective, nonrandomized study, Stop Imatinib (STIM) (NCT00478985), 100 patients in complete molecular remission stopped imatinib after more than 2 years of therapy; by 1 year, 61% of patients relapsed and all responded to the reintroduction of imatinib.[28] Longer follow-up is required to see if some patients maintain a long-term remission after discontinuation of therapy. The same investigators have shown in the According to Stop Imatinib (A-STIM) study that molecular remission can be re-established anecdotally after restarting therapy.[29]

Does time-to-response matter if a good response is obtained eventually?

Does a good response in a high-risk patient overcome the adverse prognosis of the high-risk
features?

What is the role of allogeneic BMT or SCT for younger, eligible patients and when should it be offered?[30,31]

Should other active agents be added to therapy with tyrosine kinase inhibitors?[32]

All of these issues have led to an active reappraisal of recommendations for optimal frontline therapy for chronic-phase CML.

High-dose therapy followed by allogeneic BMT or SCT

The only consistently successful curative treatment of CML has been high-dose therapy followed by allogeneic BMT or SCT.[33] Patients younger than 60 years with an identical twin or with
HLA-identical siblings can be considered for BMT early in the chronic phase. Although the procedure is associated with
considerable acute morbidity and mortality, 50% to 70%
of patients transplanted in the chronic phase survive 2 to 3 years, and the
results are better in younger patients, especially those younger than 20 years.
The results of patients transplanted in the accelerated and blastic phases of the
disease are progressively worse.[34,35] Most transplant series suggest improved survival when the
procedure is performed within 1 year of diagnosis.[36-38][Level of evidence: 3iiiA] The data supporting early transplant, however, have never been confirmed in controlled
trials. In a randomized, clinical trial, disease-free survival and OS were
comparable when allogeneic transplantation followed preparative therapy with
cyclophosphamide and total-body irradiation (TBI) or busulfan and
cyclophosphamide without TBI. The latter regimen was associated with less
graft-versus-host disease and fewer fevers, hospitalizations, and hospital
days.[39][Level of evidence: 1iiA] Reduced-intensity conditioning allogeneic SCT is under evaluation in first or second remissions.[40,41]

About 20% of otherwise eligible CML patients lack a suitably matched sibling
donor.[42] HLA-matched unrelated donors or donors mismatched at one-HLA antigen
can be found for about 50% of eligible participants through the National Marrow
Donor Program.[42] A retrospective review of 2,444 patients who received myeloablative allogeneic SCT showed OS at 15 years of 88% (95% confidence interval [CI], 86%–90%) for sibling-matched transplant and of 87% (95% CI, 83%–90%) for unrelated donor transplant.[43] The cumulative incidences of relapse were 8% (95% CI, 7%–10%) for sibling-matched transplant and 2% (95% CI, 1%– 4%) for unrelated donor transplant.[43]

Although the majority of relapses occur within 5 years
of transplantation, relapses have occurred for as long as 15 years following BMT.[44] In a molecular analysis of 243 patients who underwent allogeneic BMT over a 20-year interval, only 15% had no detectable BCR/ABL transcript by PCR analysis.[45]
The risk of relapse appears to be less in patients transplanted early in
disease and in patients who develop chronic graft-versus-host disease.[35,46]

With the advent of imatinib, dasatinib, and nilotinib, the timing and sequence of allogeneic BMT or SCT has been cast in doubt.[31] Allogeneic SCT is the preferred choice for patients presenting with accelerated-phase or blast-phase disease, for patients with a T3151 mutation (resistant to currently available tyrosine kinase inhibitors), and for patients with complete intolerance to the pharmacologic options.[47]

In a prospective trial of 354 patients aged younger than 60 years, 123 of 135 patients with a matched, related donor underwent early allogeneic SCT while the others received interferon-based therapy and imatinib at relapse; some also underwent a matched, unrelated-donor transplant in remission.[48] With a 9-year median follow-up, survival still favored the drug treatment arm (P = .049), but most of the benefit was early as a result of transplant-related mortality, with the survival curves converging by 8 years.[48][Level of evidence: 2A] Among the many unanswered questions are the following:

Does the substantial toxicity and mortality of allogeneic transplantation render its early use obsolete?

Clinical trials and long-term results from ongoing trials will be required before these controversies are resolved.

Tyrosine kinase inhibitor-resistant CML

For patients resistant to several tyrosine kinase inhibitors, omacetaxine mepesuccinate (a cephalotaxine, formerly known as homoharringtonine, with activity independent of BCR/ABL) has shown a hematologic response rate of 67% and a median PFS of 7 months in a small, phase II study of 46 patients.[49][Level of evidence: 3iiiDiv]

Hydroxyurea

Hydroxyurea is given daily by mouth (1–3 g per day as a single dose on
an empty stomach). Hydroxyurea is superior to busulfan in the chronic phase of
CML, with significantly longer median survival and significantly fewer severe
adverse effects.[50] A dose of 40 mg/kg per day is often
used initially and frequently results in a rapid reduction of the white blood
cell (WBC) count. When the WBC count drops below 20,000 mm3,
the hydroxyurea is often reduced and titrated to maintain a WBC count between
5,000 and 20,000. Hydroxyurea is
currently used primarily to stabilize patients with hyperleukocytosis or as
palliative therapy for patients who have not responded to other therapies.

Current Clinical Trials

Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with
chronic phase chronic myelogenous leukemia. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.

General information about clinical trials is also available from the NCI Web site.

Imatinib mesylate. Among 176 patients with accelerated-phase CML, the complete hematologic response was 82%, and the complete cytogenetic response was 43%; with a median follow-up of 41 months, the estimated 4-year survival was 53%.[2] Other tyrosine kinase inhibitors need to be evaluated as first-line therapy in accelerated-phase CML.

Interferon alpha.[3] Although the response rate is lower for accelerated-phase disease than it is for chronic-phase disease, durable responses and
suppression of cytogenetic clonal evolution have been reported.[3,4] When
cytarabine was added to interferon alpha, in comparison to historical controls
of interferon alone, the response rate and 3-year survival appeared to be
improved in late-stage patients.[4][Level of evidence: 3iiiA]

Patients with accelerated-phase CML show signs of progression without meeting the criteria for blast crisis (acute leukemia). Symptoms and findings include the following:

Increasing fatigue and malaise. (Refer to the PDQ summary on Fatigue for more information.)

Progressive splenomegaly.

Increasing leukocytosis and/or thrombocytosis.

Worsening anemia.

Bone marrow examination shows increasing blast cell percentage (but ≤30%) and basophilia. Additional cytogenetic abnormalities occur during the accelerated phase (trisomy 8, trisomy 19, isochromosome 17Q, p53 mutations or deletions), and the combination of hematologic progression plus additional cytogenetic abnormalities predicts for lower response rates and a shorter time-to-treatment failure on imatinib mesylate.[6] At 1 year after the start of imatinib, the failure rate is 68% for patients with both hematologic progression and cytogenetic abnormalities, 31% for patients with only hematologic progression, and 0% for patients with cytogenetic abnormalities only. Before the availability of imatinib, the median survival time of accelerated-phase CML patients was less than 1 year.[6]

Current Clinical Trials

Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with
accelerated phase chronic myelogenous leukemia. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.

General information about clinical trials is also available from the NCI Web site.

Blastic-Phase CML

Treatment Options for Blastic-Phase CML

Imatinib mesylate, dasatinib, and nilotinib have demonstrated activity in patients with
myeloid blast crisis and lymphoid blast crisis or Philadelphia
chromosome–positive acute lymphoblastic leukemia.[1,2]
Two trials of imatinib mesylate and one trial of dasatinib involving a total of 518 patients in blastic-phase chronic myelogenous leukemia (CML) confirm a hematologic response rate of 42% to 55% and a major cytogenetic response rate of 16% to 25%, but the estimated 2-year survival rate is under 28%.[2-4][Level of evidence: 3iiiA] Clinical trials will explore combining imatinib mesylate with other drugs to improve the prognosis of patients with blastic-phase CML.[5]

Vincristine and prednisone with or without an anthracycline is another treatment option (for the
approximately 25% of patients with terminal deoxynucleotidyl transferase-positive cells and lymphoblastic transformation).[6,7]

Allogeneic bone marrow transplantation (BMT) represents the only potentially curative
approach in these patients. Allogeneic BMT is more effective in
patients induced into a second chronic phase.

Current Clinical Trials

Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with
blastic phase chronic myelogenous leukemia. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.

General information about clinical trials is also available from the NCI Web site.

Relapsing CML

Overt failure is defined as a loss of hematologic remission or progression to accelerated-phase or blast-crisis phase chronic myelogenous leukemia (CML) as previously defined. A consistently rising quantitative reverse–transcription polymerase chain reaction BCR/ABL level suggests relapsing disease. For initial use of imatinib mesylate, the designation of relative failure or suboptimal response has been proposed for lack of complete hematologic remission by 3 months, no cytogenetic response by 6 months, or no major cytogenetic response by 12 months.[1,2] Nilotinib and dasatinib induce such high rates of complete cytogenetic responses and major molecular responses within several months that new benchmarks are required for responsiveness.[3] These investigators propose that a complete cytogenetic response by 3 months should define an optimal response.[4]

In case of treatment failure or suboptimal response, patients should undergo BCR/ABL kinase domain mutation analysis to help guide therapy with the newer tyrosine kinase inhibitors or with allogeneic transplantation.[5,6] Mutations in the tyrosine kinase domain can confer resistance to imatinib mesylate; alternative inhibitors such as dasatinib, nilotinib, or bosutinib, higher doses of imatinib mesylate, and allogeneic stem cell transplantation (SCT) have been studied in this setting.[7-19] In particular, the T315I mutation marks resistance to imatinib, dasatinib, nilotinib, and bosutinib. In a phase II study with 449 patients, 60% of the 129 patients with the T315I mutation had a molecular response to ponatinib, an oral tyrosine kinase inhibitor.[20][Level of evidence: 3iiiDiv] Ponatinib also has activity in heavily pretreated-resistant CML and in a third of the patients with accelerated-phase or blast-crisis phase CML.[20]

For patients resistant to several tyrosine kinase inhibitors, omacetaxine mepesuccinate (a cephalotaxine, formerly known as homoharringtonine, with activity independent of BCR/ABL) has shown a hematologic response rate of 67% and a median progression-free survival of 7 months in a small, phase II study of 46 patients.[21][Level of evidence: 3iiiDiv]

Infusions of buffy-coat leukocytes or isolated T cells obtained by pheresis
from the bone marrow transplant donor have induced long-term remissions in more
than 50% of patients who relapse following allogeneic transplant.[22,23] The efficacy
of this treatment is thought to be the result of an immunologic graft-versus-leukemia
effect. This treatment is most effective for patients whose relapse is
detectable only by cytogenetics or molecular studies and is associated with
significant graft-versus-host disease. After relapse from allogeneic SCT, some patients will
also respond to interferon alpha.[24] Most patients will respond to imatinib mesylate with durable (>1 year) cytogenetic and molecular responses. (These patients had not previously received imatinib.)[25-27]

Current Clinical Trials

Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with
relapsing chronic myelogenous leukemia. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.

General information about clinical trials is also available from the NCI Web site.

About This PDQ Summary

Purpose of This Summary

This PDQ cancer information summary for health professionals provides comprehensive, peer-reviewed, evidence-based information about the treatment of chronic myelogenous leukemia. It is intended as a resource to inform and assist clinicians who care for cancer patients. It does not provide formal guidelines or recommendations for making health care decisions.

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